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Susan K Rohde1,2,3,4, Maruelle C Luimes2,3,4, Annemieke J M Rozemuller5,6

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In centenarians, Alzheimer's disease neuropathologic change (ADNC) and primary age-related tauopathy (PART) show overlapping tau patterns, unlike in younger individuals. However, both amyloid-beta (Aβ) and tau pathologies in specific brain regions correlate with cognitive decline.

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Area of Science:

  • Neuropathology
  • Neuroscience
  • Aging Research

Background:

  • Alzheimer's disease neuropathologic change (ADNC) and primary age-related tauopathy (PART) exhibit distinct hippocampal pathology patterns.
  • PART is an amyloid-beta (Aβ)-independent tauopathy with higher CA2/CA1 hyperphosphorylated tau (pTau) ratios compared to ADNC.
  • The persistence of these distinct patterns in extreme ages and their correlation with cognition in centenarians remain unclear.

Purpose of the Study:

  • To investigate whether distinct hippocampal pTau distributions persist into extreme ages.
  • To examine the correlation between hippocampal Aβ- and pTau-distributions and cognitive function in centenarians.
  • To compare neuropathologic patterns in centenarians with ADNC versus PART.

Main Methods:

  • Quantified Aβ- and pTau-burdens in eight hippocampal and parahippocampal subregions in 112 centenarians, 11 AD, and 7 PART cases.
  • Compared CA2/CA1-pTau-ratios in centenarians meeting PART versus ADNC criteria.
  • Assessed cognitive performance using 13 neuropsychological tests and employed robust linear regression to associate pathologies with cognition.

Main Results:

  • CA2/CA1-pTau-ratios in centenarians with PART were comparable to those with ADNC, unlike in younger individuals.
  • In centenarians, CA2/CA1-pTau-ratio was unrelated to Aβ-burden, Thal phase, or Braak stage.
  • Higher hippocampal Aβ-burden and parahippocampal pTau-burden were associated with lower cognitive performance.

Conclusions:

  • In the oldest-old, PART and ADNC are less distinguishable by traditional determinants.
  • Centenarians with ADNC may exhibit Aβ accumulation with PART-like pTau patterns, while PART cases may not always show PART-like pTau patterns.
  • Hippocampal Aβ-burden and parahippocampal pTau-burden are linked to cognitive decline, indicating subregional vulnerability.